Photodynamic therapy (PDT) provides for standalone or intraoperative cancer treatment. PDT provides a means to treat superficial and/or residual disease, while minimizing damage to underlying tissues, and does not exhibit cumulative cell toxicities, distinguishing it from radiation therapy. As compared to radiotherapy, treatment planning in PDT is often approached in a one-size-fits-all fashion. However, patient- and tumor-specific factors such as tissue optical properties and photosensitizer (PS) levels are critical to the delivery of effective light doses. The development of treatment dosimetry tools tha take into account these factors will fill an unmet clinical need and provide for individualized patient treatment. An effective PDT treatment dosimetry system stands to improve therapeutic outcomes, reduce the need for repeat PDT or additional cell-killing therapy, and could therefore reduce overall costs in the per patient delivery of cancer-related therapy and care. The major objective of this SBIR Phase II proposal is to develop and verify prototype software and hardware tools that combine simulations of PS photophysics with light propagation using fast Monte-Carlo (MC) techniques. The research of this Phase II SBIR will result in unique prototype dosimetry tools that will be further developed and commercialized in Phase III for use by PDT physicians and researchers to improve patient outcomes. This Phase II SBIR has three major aims. Aim 1 is to develop prototype software for PDT dosimetry combining light transport using fast Monte-Carlo (MC) techniques and patient PS variability. The software should be fast enough for future clinical use in Phase III of this project. At the foundation of this system will e Simphotek's novel Active Photonics Building Blocks (APBB) algorithm with its simple graphical user interface for active photophysics. The APBB breaks the computing problem for photophysics into a series of computational building blocks that the software automatically combines to generate the full numerical simulation. To include light scattering in the analysis, Simphotek has partnered with Tech-X Corporation (Tech-X; subaward), a leader in the field of high-performance computing. Tech-X has developed MC-based scattering infrastructure and has adapted the code in Phase I to model light diffusion and absorption processes in biological tissue. The Aim 2 objective is for Tech-X and Simphotek to develop a prototype PDT dosimetry tool combining both the software developed in Aim 1 and specialized hardware for high-speed simulations. Aim 3 is to verify the software/hardware simulations by comparing the simulation results to phantom measurements done at the University of Pennsylvania School of Medicine (Penn; subaward) by experts in PDT.